Summaries of newsworthy papers include Breaking through the barrier, Clearing plaques in blood vessels in Alzheimer’s disease, Agriculture could increase the release of carbon dioxide from rivers, Prions and smell, Rotoviruses stick to sugars, Tropical volcanic eruptions drive cooling in the tropics, The twisted history of snail shells

NATURE AND THE NATURE RESEARCH JOURNALS PRESS RELEASE

For papers that will be published online on 21 December 2008

This press release is copyrighted to the Nature journals mentioned below.

Geoscience: Agriculture could increase the release of carbon dioxide from rivers

Neuroscience: Prions and smell

Chemical Biology: Rotoviruses stick to sugars

Geoscience: Tropical volcanic eruptions drive cooling in the tropics

And finally… Nature: The twisted history of snail shells

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[1] Nature: Stem cells and disease modelling
DOI: 10.1038/nature07677

Scientists have generated pluripotent stem cells from the skin cells of a patient with spinal muscular atrophy (SMA), and show that these cells can be used to model the specific pathology for inherited diseases. The research, published online in Nature this week, represents a promising tool for understanding disease at a cellular level and also for drug screening.

SMA is a genetic disorder, and one of the most common inherited forms of neurological disease in children. Allison Ebert and colleagues use skin cells from a child with SMA and his unaffected mother. They show, for the first time, that human induced pluripotent stem cells can be used to model the disease mechanisms, as the differentiated neural tissue and motor neurons derived from these cells maintain the disease phenotype. The cultures also responded to drugs known to increase the levels of the protein associated with the disease. This creates a tool for studying disease pathology at the cellular level, and for developing and screening new drugs and therapies.

A non-invasive method to deliver genes to the central nervous system in mice is reported online this week in Nature Biotechnology. The research could one day lead to new therapies for neurodegenerative disorders such as Lou Gehrig’s disease.

Getting drugs or genes into the brain and spinal cord to treat neurodegenerative diseases is problematic because of the blood–brain barrier (BBB)—a tight wall of cells that restricts the movement of molecules between the blood and neural tissue. Until now, no viruses or viral vectors have been found that cross through the BBB after intravascular injection. Brian Kaspar and colleagues show that a particular strain of virus – AAV9 – can be used to carry genes across the BBB in mice and into the brain cells beyond. The team also find that the virus targets cells of the spinal cord and so can be used to deliver genes to widespread regions of the central nervous system.

It is hoped that the technology could one day be used to introduce working copies of the genes that are damaged in diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease.

Scientists have uncovered the role of two critical proteins that negatively affect the clearance of amyloid beta in the brain, the accumulation of which is thought to lead to the development of Alzheimer’s disease. The research, published online in Nature Cell Biology this week, identifies potential therapeutic targets for treating defects associated with cognitive decline and faulty clearance of amyloid beta in brain blood vessels.

The exact causes of Alzheimer’s disease are still unclear. Previous studies have shown that the disease is associated with plaques or tangles of protein fragments in the brain. These fragments, known as amyloid beta, accumulate in small arteries of the brain and contribute to the defects that occur during Alzheimer’s disease.

Berislav Zlokovic and colleagues examined the effect of two interacting proteins, SRF and MYOCD, which bind to DNA and control gene expression. They show that these proteins are highly expressed in blood vessel cells in Alzheimer’s patients and in mouse models of the disease, and that high levels of these proteins prevent the clearance of amyloid beta from vessel walls. These proteins act by activating a third protein that regulates gene expression and is known to prevent the expression of the lipoprotein receptor protein 1, a factor that promotes clearance of amyloid beta in blood vessel cells.

Intensive agriculture decreases the chemical complexity of dissolved organic matter in nearby rivers, suggests a paper online in Nature Geoscience. Simplification of organic material could affect the release of carbon dioxide from river systems.

Henry Wilson and colleagues examined the quality of organic matter dissolved in 34 rivers in Ontario, Canada, along a gradient of minimal-to-intensive agriculture. The researchers found that higher levels of cropland cultivation and usage resulted in a decrease in the structural complexity of the dissolved organic matter in the river. They suggest that the reduced complexity of organic matter could lead to elevated rates of microbial carbon-processing. As a result organic matter may be more readily removed from rivers — either through storage in sediments or through release into the atmosphere as carbon dioxide.

Prions help us to distinguish odours, finds a study published online this week in Nature Neuroscience. The research provides tantalizing clues as to the normal function of these mysterious proteins.

Prions are proteins involved in devastating diseases such as Creutzfeld-Jacob Disease (CJD) and Bovine Spongiform Encephalopathy (BSE) but little is known about how they normally function. Stuart Firestein and colleagues studied transgenic mice that lacked the prion protein in neurons of the olfactory system – the part of the brain that controls our sense of smell. They find that these mice could still detect odours, but were deficient in some odour-guided behaviours such as finding buried food or an odour discrimination task. Replacing the protein in olfactory bulb neurons alone rescued this odour discrimination defect. The authors also find specific changes in the communication among neurons in the olfactory bulb of these transgenic mice.

It is not clear how these changes in odour discrimination relate to the pathology of prion diseases, but the research provides greater understanding of these enigmatic proteins.

Sugar molecules on the surface of host cells are linked to all rotovirus infections, according to research published online in Nature Chemical Biology this week. The unexpected finding promises to aid efforts to develop treatments for this dangerous virus.

Rotoviruses attack cells of the gut and are the leading cause of severe diarrhea in young children. Many animals can be treated for the virus with a protein called sialidase, which cuts sialic acids – a specific group of sugar molecules – from the cell surface. Unsuccessful attempts to treat other rotoviruses with this protein resulted in the rotoviruses being grouped into two classes of ‘sialidase-sensitive’ and ‘sialidase-insensitive’ strains.

Mark von Itzstein and colleagues use nuclear magnetic resonance and cellular assays to demonstrate that a ‘sialidase-insensitive’ virus strain, Wa, does recognize sialic acids and in fact this interaction increases its ability to infect the host cell. The research demands a rethinking of how rotoviruses work and may point to new treatments for the infection.

Over the past 450 years, the aerosols and gases emitted from volcanic eruptions in the tropics have caused tropical sea-surface temperatures to cool for years after the eruption, according to a study online in Nature Geoscience. Although a similar relationship has been observed in the high northern-latitudes, this is the first time a consistent pattern has been observed in the tropics.

Rosanne D’Arrigo and colleagues compiled temperature records from corals and tree rings throughout the Indian and Pacific oceans. Like the well-known cooling that followed the 1815 Tambora eruption in Indonesia, a clear correlation was found between the most explosive volcanic eruptions at low latitudes and decreased sea-surface temperatures in the following years. The team concludes that the relationship between eruptions and sea-surface cooling highlights the sensitivity of tropical temperatures to the amount of sunlight reaching the Earth’s surface.

[8] And finally… Nature: The twisted history of snail shells
DOI: 10.1038/nature07603

The direction of snail shell coiling is regulated by nodal, a gene well known for its role in vertebrate body patterning. The find, reported online in this week’s Nature, sheds light on the evolutionary history of this signalling pathway.

Cristina Grande and Nipam Patel show that evolutionary equivalents of the nodal gene are present in two species of snail. The gene is expressed asymmetrically during embryonic development in a manner correlating with the direction of shell coiling, and blocking the pathway produces animals with non-coiled shells.

Until now, nodal was generally regarded as an invention of the deuterostomes — the group of animals that includes vertebrates, starfish and some worms — where it influences left–right asymmetry. The new data indicate that the role of the gene in left–right asymmetry is not deuterostome-specific and may be an ancestral feature of bilaterally symmetrical animals.

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Items from other Nature journals to be published online at the same time and with the same embargo:

The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

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